The safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine among patients undergoing elective surgery for closed fractures: A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial.

BACKGROUND: Vaccines are urgently required to control Staphylococcus aureus hospital and community infections and reduce the use of antibiotics. Here, we report the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in patients undergoing elective surgery for closed fractures. METHODS: A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial was carried out in 10 clinical research centers in China. Patients undergoing elective surgery for closed fractures, aged 18-70 years, were randomly allocated at a ratio of 1:1 to receive the rFSAV or placebo at a regimen of two doses on day 0 and another dose on day 7. All participants and investigators remained blinded during the study period. The safety endpoint was the incidence of adverse events within 180 days. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as opsonophagocytic antibodies. RESULTS: A total of 348 eligible participants were randomized to the rFSAV (n = 174) and placebo (n = 174) groups. No grade 3 local adverse events occurred. There was no significant difference in the incidence of overall systemic adverse events between the experimental (40.24 %) and control groups (33.72 %) within 180 days after the first immunization. The antigen-specific binding antibodies started to increase at days 7 and reached their peaks at 10-14 days after the first immunization. The rapid and potent opsonophagocytic antibodies were also substantially above the background levels. CONCLUSIONS: rFSAV is safe and well-tolerated in patients undergoing elective surgery for closed fractures. It elicited rapid and robust specific humoral immune responses using the perioperative immunization procedure. These results provide evidence for further clinical trials to confirm the vaccine efficacy. China's Drug Clinical Trials Registration and Information Publicity Platform registration number: CTR20181788. WHO International Clinical Trial Registry Platform identifier: ChiCTR2200066259.

Osteopenia and fractures associated with long-term therapy with MEK inhibitors.

Targeted therapies have markedly improved the survival of patients with melanoma. We report the case of two patients with advanced melanoma controlled by long-term MEK inhibitor or combination of BRAF and MEK inhibitors, who developed fractures related to severe osteopenia. A 48-year-old woman was treated by pimasertib after the failure of two lines of chemotherapy, and a 42-year-old man was treated by an association of BRAFi (dabrafenib) and MEKi (trametinib) after the failure of one line of chemotherapy. During follow-up, both complained of buttock pain, revealing primary fractures of the pelvis and lumbar vertebra. In both patients, none had osteoporosis risk factors; DEXA scan revealed osteopenia, and analysis ruled out metastatic bone lesion or secondary osteoporosis. Zoledronic acid, cholecalciferol (vitamin D3), oral calcium, and pain killers were introduced, leading to no further bone event. Numerous pathways are involved in the homeostasis of bone turnover, and the effect of tyrosine kinase inhibitors on those pathways is not well known yet. The absence of usual causes of osteoporosis or metastatic bone lesion and kinetics of symptoms lead us to suggest that MEK inhibitors were responsible for the development of osteoporosis. To the best of our knowledge, this is the first report of fractures associated with osteopenia in patients treated with MEKi. Long-term survival owing to new targeted treatment could be associated with yet underestimated adverse effects such as osteopenia/osteoporosis that could impair patient's quality of life and should be investigated.

[Fractures of the calcaneus during fluoride therapy of osteoporosis]. / Fractures du calcanéum au cours du traitement de l'ostéoporose par le fluor.

Two cases of calcaneum "stress" fractures are reported. The fracture, which was unilateral in the first case and bilateral in the second, occurred 15 and 18 months respectively after the initiation of fluoride treatment for osteoporosis. The simultaneous discovery of thyrotoxicosis in the second patient suggests that the role of hyperthyroidism in the occurrence of these fractures be discussed in addition to that of fluoride treatment.